ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

I haven't come across PrEP before - it is not easily accessible in Western Australia, although a few patients have obtained it through personal importation. Hence, the sessions on PrEP were of particular importance to me as I'm sure they will be filtering through to WA very soon. In particular I enjoyed the summary by Prof Jared Baeten, and I've tried to summarise my learning points below. I've combined two of his talks into one.

Firstly, I love this quote that he put up (forgotten who said it though): all truth goes through three phases: it is ridiculed, violently opposed, and then accepted as self-evident.

PrEP works: those who had tenofovir in their system had a >90% reduction in HIV transmission

PrEP works for high risk patients

a single agent may work as well as dual agents (e.g. TDF only = 85%, TDF/FTC = 93%)

adherers adhere

not everyone used PrEP, but those who did use it tended to be consistent users

non-adherers rarely started adhering

there wasn't much change in behaviour after 1 month

surprisingly, real world effectiveness was better than efficacy in the studies

?adherence was better in real life than in the trials

PrEP has several additional benefits

decreased anxiety

increased communication and trust

increased sexual pleasure and intimacy

chance of developing eGRF <70 while on PrEP if your baseline is >90 is extremely small

rising STI rates in the US have been happening for a while, even before the introduction of PrEP

PrEP works even when STIs are present

Most of the informal feedback I've heard before today has been that PrEP is associated with an increase in STIs but if the data above is applicable to Australia, then perhaps that isn't quite true. I think the evidence if favour of PrEP is mounting, and the major obstacle in Australia is probably the cost-benefit ratio...

As PrEP has now been used in the USA for about six years, Dr Jared Baeton compared PrEP to the developmental milestones reached by the average six year-old child.

At six years old, we begin to understand cause and effect relationships.

If you take PrEP, it works. As in, if you have good adherence, then it is close to 100% effective at preventing HIV transmission. Interestingly, studies have shown that those individuals at greatest risk of HIV appear to have a greater HIV risk reduction from PrEP. This suggests that those individuals at greatest risk of HIV also have the greatest adherence to PrEP.

At the age of six, magical thinking fades quickly: PrEP is not perfect, and PrEP does not expect us to be perfect.

PrEP is not perfect, but PrEP is safe. We have good data on kidney safety and bone safety for PrEP users. Also the risk of antiretroviral resistance appears to be limited to those who start PrEP in the context of an acute HIV infection, rather than those who seroconvert during PrEP use. He did not further expand on this thought, but perhaps those who seroconvert during PrEP use have such low adherence to PrEP that it does not result in the selection of resistant HIV variants.

PrEP does not expect us to be perfect. In clinical trials, not everyone used PrEP, but those who did use it tended to be consistent users (Partners PrEP). Those who were not adherent at one month tended to never become adherent. Dr Baeton drew an analogy between PrEP adherence and flossing: Some of us floss every day, and tend to continue doing so, others rarely floss and never start flossing regularly.

The average six year-old starts to understand the feelings of others. As a medical community we’re starting to understand what PrEP users want out of PrEP. And PrEP use has been shown to be associated with:

Decreased anxiey

Increased communication, trust, and HIV status disclosure

Increased self-efficacy

Increased sexual pleasure and intimacy

Stigma remains a key barrier to PrEP use: This includes stigma about ARVs, HIV and stigma about being at risk of HIV.

4. Six year-olds become more flexible in their thinking:

Success in PrEP adherence is achieved when PrEP is used during times of HIV exposure, this has been referred to as “prevention-effective adherence”. I think we need to develop some clear messaging around “prevention-effective adherence”, to assist people in

STIs will occur in persons using PrEP. People who need PrEP are at hight risk of STIs.

PrEP makes us think very differenctly about three decades of fear-based public health campaigns.

5. 6 year-olds start to understand more about his/her place in the world. PrEP is not a panacea, but it has the potential to form an important part of the toolbox of HIV prevention.

I think PrEP has come a long way over the last couple of years, including in Australia. In order to continue this trajectory, I think we need ongoing efforts to:

1. Obtain PBS-listing for PrEP

2. Prevent the emergency of PrEP-associated stigma, by framing the discussion around PrEP in a sex-positive manner.

3. Develop clear messaging around dosing regimens that do not involve daily PrEP. Some people do not need to be on PrEP continuously, and we need to have realistic conversations how these people can effectively manage their HIV risk without necessarily taking PrEP every day.

Day 4’s morning session was focused largely on PrEP, making it interesting and relevant to the Australian context.

Chloe Orkin (from the Royal London Hospital) began by providing a brief summary of the current situation and future prospects for PrEP.

She noted the current use (as PrEP) of standard antiretrovirals; the development of new compounds from existing classes (e.g. EFdA [NRTI]; dapivirine, MIV-170 and IQP-0528 [NNRTIs]; cabotegravir and MK-2048 [IIs]; and entry inhibitors [vivriviroc, 5P12-RANTES, PIE-12, nifviroc and trimer-D-peptide]); as well as new compounds from new classes (VRC01 and griffithsin [Neutralising antibodies]).

Sheena McCormack (University College London) presented an update on the evidence for PrEP effectiveness.

She began by presenting the a summary of currently available evidence as below, reminding us that overall (especially in MSM) PrEP is very effective; that adherence was a major factor in many of the studies where effectiveness was less good (particularly in young black MSM in the USA and in heterosexual populations).

She focused on the PROUD (continuous truvada as PrEP; immediately or deferred) study which looked at effectiveness, risk compensation and STI rates This study showed an effectiveness of 86% (90% CI 64-96%), with NNT = 13 (90% CI 9-23) – Dr McCormack commented that this compares favourably with other medications (such as statins) that’re approved for preventive measures. She also commented that some of those in the immediate intervention (PrEP) arm had significantly more unprotected anal intercourse than those in the deferred arm, and that rates of unprotected anal intercourse in both arms were relatively high. In that study, a rectal STI indicated a 1 in 6 risk of HIV infection in the following year.

Australia’s EPIC study was mentioned, particularly with regard to the fact that it targeted those at high risk of HIV.

She provided a summary of worldwide PrEP demonstration projects between 2011-2015:

-32 projects in 16 countries

-8478 participants with 7061 cumulative years exposure

-Total HIV seroconversions n=67

à Highest rates in MSM 18-25 years (7.7/100 person-years)

à However available intracellular data showed undetectable or very low tenofovir levels in nearly all of those with seroconversion while on PrEP.

Episodic vs daily dosing – the importance of choice to effectiveness

HPTN 067/ADAPT study was mentioned: this study compared the use of daily, twice weekly (and another tablet after sex) and episode-driven PrEP in 3 populations (Harlem MSM/TGW; Bangkok MSM/TGW; Cape Town WSM). It showed that in the Bangkok population (who were generally better educated and suffered less social disadvantage) there was little difference in effectiveness between treatment arms, whereas adherence was much poorer for event-based PrEP in the other two arms (compared with continuous PrEP). This suggests that a choice of event-based or continuous PrEP may be useful depending on the population in question, and that if a population is likely to be adherent to episodic PrEP, this may produce cost-savings (less drug used overall).

HIV infection despite PrEP

Those two cases of HIV being contracted despite good adherence (and adequate drug levels) were mentioned, including the “Toronto case” and the second case recently reported of a MSM acquiring a strain of resistant HIV. This reinforces the importance of reminding those on PrEP that it is not 100% effective.

Possible use of maraviroc as PrEP

HPTN 069/ACTG 5305 (Phase II Study of Maraviroc-Based Regimens for HIV PrEP in MSM) was discussed. In this study of n=406 MSM, people were randomised to oral maraviroc (MVC) only; MVC+FTC; MVC+TDF or TDF+FTC. 5 seroconversions occurred (4 in MVC-only arm), but in 4 of those plasma drug levels were low or undetectable.